αβ T-cell graft depletion for allogeneic HSCT in adults with hematological malignancies.

Autor:	de Witte MA; Department of Hematology and., Janssen A; Department of Hematology and.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Nijssen K; Department of Hematology and., Karaiskaki F; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Swanenberg L; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., van Rhenen A; Department of Hematology and., Admiraal R; Paediatric Blood and Marrow Transplant Program, Princes Maxima Center for Pediatric Oncology, Utrecht, The Netherlands., van der Wagen L; Department of Hematology and., Minnema MC; Department of Hematology and., Petersen E; Department of Hematology and., Raymakers RAP; Department of Hematology and., Westinga K; Cell Therapy Facility, University Medical Center Utrecht, Utrecht, The Netherlands., Straetemans T; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Halkes CJM; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands; and., Boelens JJ; Stem Cell Transplantation and Cellular Therapies, MSK Kids, Memorial Sloan Kettering Cancer Center, New York, NY., Kuball J; Department of Hematology and.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2021 Jan 12; Vol. 5 (1), pp. 240-249.
DOI:	10.1182/bloodadvances.2020002444
Abstrakt:	We conducted a multicenter prospective single-arm phase 1/2 study that assesses the outcome of αβ T-cell depleted allogeneic hematopoietic stem cell transplantation (allo-HSCT) of peripheral blood derived stem cells from matched related, or unrelated donors (10/10 and 9/10) in adults, with the incidence of acute graft-versus-host disease (aGVHD) as the primary end point at day 100. Thirty-five adults (median age, 59; range, 19-69 years) were enrolled. Conditioning consisted of antithymocyte globulin, busulfan, and fludarabine, followed by 28 days of mycophenolic acid after allo-HSCT. The minimal follow-up time was 24 months. The median number of infused CD34+ cells and αβ T cells were 6.1 × 106 and 16.3 × 103 cells per kg, respectively. The cumulative incidence (CI) of aGVHD grades 2-4 and 3-4 at day 100 was 26% and 14%. One secondary graft failure was observed. A prophylactic donor lymphocyte infusion (DLI) (1 × 105 CD3+ T cells per kg) was administered to 54% of the subjects, resulting in a CI of aGVHD grades 2-4 and 3-4 to 37% and 17% at 2 years. Immune monitoring revealed an early reconstitution of natural killer (NK) and γδ T cells. Cytomegalovirus reactivation associated with expansion of memory-like NK cells. The CI of relapse was 29%, and the nonrelapse mortality 32% at 2 years. The 2-year CI of chronic GVHD (cGVHD) was 23%, of which 17% was moderate. We conclude that only 26% of patients developed aGVHD 2-4 after αβ T-cell-depleted allo-HSCT within 100 days and was associated with a low incidence of cGVHD after 2 years. This trial was registered at www.trialregister.nl as #NL4767. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
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